International Delphi consensus recommendations for the follow-up of children born to people with CF and exposed to CFTR modulators in utero or through breastfeeding; endorsed by the European Cystic Fibrosis Society.

BACKGROUND

Pregnancies among people with cystic fibrosis (PwCF) have increased in the CFTR modulator (CFTRm) era. However, pregnant PwCF were excluded from CFTRm trials, limiting evidence on offspring outcomes after in utero and breast milk exposure. Follow-up practices for exposed children vary, and no widely accepted recommendations exist. We aimed to develop the first international recommendations for clinical follow-up of children exposed to CFTRm in utero and/or via breastfeeding.

METHODS

An international survey of follow-up practices and a literature review informed item generation for a Delphi consensus survey. We recruited panellists from four clinician groups (paediatric CF, adult CF, non-CF physicians, and other healthcare professionals) and a group of PwCF. An a priori consensus threshold was set at ≥70 % overall agreement and ≥50 % agreement within each group, with up to three survey rounds. The Imperial College Research Ethics Committee granted ethical approval. The protocol was prospectively registered (DOI:10.17605/OSF.IO/VJ2Z8).

RESULTS

Completed responses were submitted by 106, 101 and 107 panellists in rounds 1-3, respectively, representing 26 countries. Clinician panellists had a median of 18 years' clinical experience (IQR 10-25). Eight PwCF participated. Consensus was reached on 73 items, including follow-up setting, liver function monitoring, cataract screening, and potential false-negative CF newborn screening. In total, we received 941 free-text comments which we used to refine existing items and generate new ones for subsequent rounds.

CONCLUSION

International consensus recommendations are now available to support consistent, implementable follow-up of children exposed to CFTRm in utero and/or via breastfeeding, adaptable to local practice.